S Mintjens1, M D Menting2, R J B J Gemke3, M N M van Poppel4, M van Wely5, A J Bensdorp6, R I Tjon Kon Fat7, B W J Mol8, R C Painter9, C van de Beek10, T J Roseboom11. 1. Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Paediatrics, Department of Gynaecology and Obstetrics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands; NYC Health and Hospitals/Lincoln, Department of Pediatrics, Room 4-20, 234 East 149(th) Street, Bronx, NY, 10451, United States. Electronic address: s.mintjens@amsterdamumc.nl. 2. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.d.menting@amsterdamumc.nl. 3. Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Paediatrics, Department of Gynaecology and Obstetrics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Electronic address: rjbj.gemke@amsterdamumc.nl. 4. Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands; University of Graz, Institute of Sport Science, Mozartgasse 14, 8010 Graz, Austria. Electronic address: mireille.van-poppel@uni-graz.at. 5. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.vanwely@amsterdamumc.nl. 6. Utrecht UMC, University of Utrecht, Department of General Health, Julius Center, Broederplein 43, 3703 CD Zeist, the Netherlands. 7. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands. 8. Department of Obstetrics and Gynecology, Monash University, Monash Medical Centre, 246 Clayton Road, Clayton Victoria 3168, Australia. Electronic address: ben.mol@monash.edu. 9. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development Research Institute, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands. Electronic address: r.c.painter@amsterdamumc.nl. 10. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: c.vandebeek@amsterdamumc.nl. 11. Amsterdam UMC, University of Amsterdam, Department of Obstetrics and Gynaecology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam Reproduction and Development Research Institute, Amsterdam Public Health Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: t.j.roseboom@amsterdamumc.nl.
Abstract
OBJECTIVE: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? STUDY DESIGN:Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. RESULTS: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. CONCLUSIONS: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.
RCT Entities:
OBJECTIVE: Does ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction affect neurodevelopmental and physical health of the offspring? STUDY DESIGN: Infertile couples were randomly allocated to intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH), modified natural cycle in vitro fertilization (IVF-MNC) or single embryo transfer IVF (IVF-SET). We compared neurodevelopmental and physical health in childhood (4-7 years). We used age-appropriate questionnaires to assess behavioral problems (Child Behavior Check List (CBCL)) and executive functioning (Behavior Rating Inventory of Executive Function (BRIEF)). We measured body mass index Z-score, waist- and hip-circumference, body fat percentage, blood pressure Z-scores, pulse wave velocity, glucose, insulin, insulin resistance, total cholesterol, high- and low-density lipoprotein cholesterol, triglycerides, and high sensitivity c-reactive protein. We compared groups by analysis of variance. RESULTS: We examined 191 (57%) of the 333 children born in the study at a mean age of 5.5 years (range 4.0-7.6 years). We found no statistically significant differences between randomization groups in children's neurodevelopmental or physical health indices (all p-values > 0.05). Comparing the outcomes between actual method of conception, including a naturally conceived group, also did not show statistically significant differences. CONCLUSIONS: Although this follow-up study was not powered on childhood outcomes and limited power due to attrition may have hampered detection of subtle effects, we found no indications of differences in neurodevelopmental and physical health between ovarian hyperstimulation and/or the in vitro procedure of assisted reproduction. Future trials should be powered on child outcomes, and aim to optimize follow-up rates to provide answers that are more definitive.
Authors: Edwina H Yeung; Pauline Mendola; Rajeshwari Sundaram; Tzu-Chun Lin; Miranda M Broadney; Diane L Putnick; Sonia L Robinson; Kristen J Polinski; Jean Wactawski-Wende; Akhgar Ghassabian; Thomas G O'Connor; Robert E Gore-Langton; Judy E Stern; Erin Bell Journal: Fertil Steril Date: 2022-06-10 Impact factor: 7.490